High-throughput screening (HTS) is a method for the rapid and accurate analysis of large numbers of chemical compounds for activity against selected targets. Typical chemical libraries contain hundreds of thousands to millions of separate compounds that are screened against a wide variety of targets. The large numbers of assays that must be routinely screened has led to a requirement for new technologies capable of rapid and quantitative analysis of small amounts of fluidic samples.
Often, the small samples to be processed in HTS are initially stored in a plurality of small wells formed in a microplate. The microplate, which is typically made of polypropylene or other plastic, may vary in size, and include any number of wells. For example a standard microplate may have a dimension of 128 mm×86 mm×14 mm and include 96, 384, or 1536 wells, with each well having an opening diameter of 1–7 mm and a working volume of 3–300 μl.
After the samples are loaded in their respective well, the microplate is typically sealed, so as to preserve the sample. Preventing evaporation of the sample can be critical, especially when such small amounts of fluidic samples are involved. The seal may be a foil, such as aluminum foil, which may be attached to the plate via a pressure sensitive adhesive (PSA) and/or a heat seal. Once sealed, the microplate can be stored for incubation and/or transferred to a test site for further processing.
To further process the samples sealed in the microplate wells, it is often required to transfer a given sample from the microplate to an analyzer, such as a mass spectrometer and/or a chromatography column. This can be accomplished by puncturing the seal of a particular well and aspirating the sample from the well to the desired destination.
However, problems arise when attempting to remove the sample from its respective well. To aspirate the sample from the well, a tube having a small diameter compatible with the size of the well is required. If the tube is too flexible, such as a tube made of Teflon, the tube will not be able to puncture the seal covering the well. Instead, upon contacting the seal, the Teflon tube will simply bend.
Alternatively, a tube made of a material capable of puncturing the seal, such as stainless steel, often is not chemically compatible. A major concern in maximizing sample throughput is the elimination of sample-to-sample carryover. Stainless steel is not a particularly bio-inert substrate and tends to strongly adsorb hydrophobic compounds in its surface. Hence, prior to aspirating the next sample, a stainless steel syringe must be thoroughly washed to prevent carryover of sample. When dealing with a large number of samples, the additional time required to thoroughly wash the stainless steel syringe, compared to a syringe made of a bio-inert substrate, can become a time consuming limitation on the system. To minimize carry-over, various hydrophobic surface coatings may be applied to the surface of the syringe, however the durability of these surface coatings is limited.